Osteoarthritis and rheumatoid arthritis are the most common joint diseases of mankind. To date, no infectious agent has been convincingly associated with rheumatoid arthritis or osteoarthritis, although preliminary data ,suggest an association with human retrovirus-5, a newly identified retrovirus. That human retrovirus-5 is associated with both rheumatoid arthritis and osteoarthritis is, on initial consideration, striking, because these diseases are felt to be epidemiologically, clinically and pathologically distinct. However, it is possible that rheumatoid arthritis and osteoarthritis are both associated with human retrovirus-5, but that the immunologic response to the infection differs in each instance. The response may depend on the genetic background of the patient. Alternatively, genetic polymorphisms amongst human retrovirus-5 isolates may account for its association with two, seemingly unrelated, disease processes. The purpose of this proposal is to establish the association of human retrovirus-5 with rheumatoid arthritis and osteoarthritis, and to further characterize human retrovirus-5 by sequencing the entire viral genome and culturing the putative retrovirus. To achieve these goals, three specific aims are proposed. Specific Aim 1: Study the association of human retrovirus-5 with rheumatoid arthritis and osteoarthritis. Specific Aim 2: Sequence the entire viral genome of human retrovirus-5. Specific Aim 3: Culture human retrovirus-5. Intraoperative synovial tissue and whole blood specimens from 50 patients with rheumatoid arthritis and 50 patients with osteoarthritis, and synovial tissue specimens from 15 patients with normal joints will be collected and tested by nested polymerase chain reaction for human retrovirus-5 proviral DNA. Positive samples will be sequenced. The frequency of detection of human retrovirus-5 proviral DNA in synovial tissues and blood from rheumatoid arthritis and osteoarthritis patients will be compared to that in patients with no known joint disease. These samples will be used as sources of human retrovirus-5 in experiments to extend the known sequence of the human retrovirus-5 genome and culture the novel virus. Identification of a specific infectious agent associated with these arthritides would potentially allo for the development of preventive strategies such as vaccination and novel therapeutic approaches.